We do have patients in post-transplant maintenance, both in the monotherapy and in the combination setting. So as — the way we’re doing this is, our studies now permit physicians to put their patients back on ziftomenib post-transplant, if they’re in the various studies. The IST that I referenced is a dedicated study that would be a lead into a dedicated post-transplant maintenance study, which would be independent and essentially agnostic to where those patients come from. Those two strategies would then marry up to make sure that you can take patients from the front line all the way through to the maintenance setting without interruption. That’s our — that’s the bigger picture strategy.
Reni Benjamin: Got it. Thank you for that added clarity. Just switching gears a little quick to 2806. When I look at KURRENT-HN and the potential to complete enrollment in the two expansion cohorts, and still identify the optimal biologically active dose in — by the end of 2024. Is — can I take that kind of a time line and apply it to 2806 or is 2806 such a unique molecule and very different from tipi that maybe that entire enrollment of the combination studies is going to be a lot quicker, we might see data a lot faster than we’re seeing in KURRENT-HN.
Troy Wilson: Sure. Yeah. So I would be hesitant to draw conclusions across trials about enrollment. The KURRENT-HN trial, the one you’re referring to is it’s a handful of size. It’s a signal-seeking study really intended to answer the question is one plus one equal to three. Tipifarnib 1, alpelisib 1, do you get better activity than either drug as monotherapy. I’ll remind everybody, you don’t expect to see really responses from either tipifarnib or alpelisib in PIK3CA-mutant head and neck. The work that’s been done with alpelisib largely resulted in stable disease, and you wouldn’t expect tipifarnib to have activity in that genotype in head and neck. So the fact that we’re seeing activity at multiple doses and that we have manageable safety, tolerability and activity to justify some dose optimization, I think, is a good — it says we may be able to extend beyond the work that we did with tipi as a monotherapy and open up that patient population.
But it’s also, I think, highly derisking of what you should expect with 2806. Because if you can combine with alpelisib, it gives you confidence that you can combine with whether it’s adagrasib, cabozantinib or something else, it’s giving us confidence that you want 2806 to be a new and improved tipifarnib. The final thing, Ren, is we don’t want to go too fast. I know that sounds counterintuitive. It’s actually a very good question. If there’s an opportunity in head and neck, do you go with tipi or do you go with 2806. And I would say our primary focus with 2806 right now is renal cell carcinoma and KRAS-driven tumors. There are — I don’t even know how many KRAS inhibitors either in the clinic or steaming into the clinic, they will all have the same issue.
They will all have innate and adaptive resistance. We’re trying to come up with an approach that basically cuts that off at the needs. And if we can demonstrate with adagrasib, then we’re going to have the high-class problem of which of these solid tumor indications do we pursue. We’ve been, Ren, very data-driven with current and just letting the patient experience sort of guide us on where to go. We’re encouraged, the physicians are encouraged, the response rate in that setting is like 20% in second line, it’s 5% or less in third line. It is as bad as pancreatic cancer. So the fact that we’re seeing, I think, encouraging clinical activity is a good thing. It’s just too early, Ren to say what’s the development strategy? Is it 2806?
Is it tipifarnib? It’s — I think it does go away toward derisking the overall program. And again, if we can pull this off, you’re talking about some big solid tumors. The 2806 trial is a dose-escalation study. And those always have their own challenges. But again, I wouldn’t draw conclusions of one disease type to the other. Our clin-ops team has been exceptional across the board from zifto to 2806, to KURRENT. They’re making good progress with the FIT-001 trial. We’ll likely share data next year on that study. I think it’s probably a little too early to show anything on FIT here in ‘24.
Reni Benjamin: Excellent. Thanks for taking the questions.
Troy Wilson: Sure.
Operator: Thank you. Your next question comes from Justin Zelin, BTIG. Justin, please go ahead.
Justin Zelin: Thanks for taking the questions. Troy, just with the KOMET-001 enrollment completion coming up here. Any thoughts on when we could see data from that study? Could that be a 2024 event or in 2025?
Troy Wilson: Yeah. Justin, let us — I know this is going to be a bit unsatisfying, let us complete enrollment. We’ve said we’re very close. Let us complete that, and then we can give you guidance on kind of what to expect. I want to make sure we do this in the right time and the right place. We obviously want to give the trial per protocol needs six months plus the time to clean the data. I think we’ll be able to answer that question better coming on the back of full enrollment.
Justin Zelin: Great. That makes sense to me. And just on 2806, could we expect additional studies with other combination agents in the future or are you pretty comfortable with what you have right now? Thanks.
Troy Wilson: Yeah. There’s certainly a rationale, Justin, to combine with other drug candidates. I think what we want to do is — and I’m going to just — for 30 seconds, just go a level deeper. The big takeaway from the current study is that you’re driving activity in that setting, both by blocking wild-type HRAS and we think by blocking farnesylation of RHEB. RHEB stands for Ras homolog expressed in brain. Why do I call that out? I called that out because that — if you look at the posters that we’ve presented, RHEB — defarnesylation or removal of the farnesyl group from RHEB is critical to blunting the innate and adaptive resistance that arises to KRAS inhibitors. And as I said, if you inhibit KRAS, the tumor is going to do a number of different things to try to escape.
One of them is to upregulate PI3 kinase signaling through that pathway, blocking RHEB farnesylation is critical to blunting that effect. So if we can block RHEB in current with one combination, it gives us confidence that we’re going to be able to block it in a different context with a KRAS inhibitor. If that’s true, and we see activity and I will tell you, initially, Mirati, now Bristol have been great clinical collaborators on this study. They’ve been very supportive. They’ve given us great input. You could imagine, Justin, using an FTI in combination with almost any KRAS inhibitor. That’s how fundamental that biology is. It’s on par with SHIP2 with SOS1, that’s how you think about it. And it’s taken us a number of years to get there, but that’s the highest — probably the highest best use, most valuable application of an FTI.
Justin Zelin: Great. Thanks for taking my questions.
Operator: Thank you. Your next question comes from George Farmer, Scotiabank. George, please go ahead.
George Farmer: Hi. Thanks for taking my question. I have two. Troy, could you address what you think the hurdles are for zifto approval in NPM1 in relapsed/refractory setting. It’s the first question. The second question is how you think about resource allocation when developing zifto in earlier lines of therapy combining with 7+3 or ven/aza?
Troy Wilson: Yeah. Can you ask the first part of the question again? I just want to make sure I’ve got — the second part is resource allocation. The first part was the hurdle rate or is that right?
George Farmer: Yeah. What do you think the hurdles are for FDA approval of zifto, refractory?
Troy Wilson: Sure. Yeah. So I think — we think that the hurdle rate for the NPM1 cohort, the same is true for KMT2A, by the way. We’ve consistently said for approval, our view is you need 20% to 30% CR/CRH four months to six months median duration of response. Would you like to do better? Yes. But we’ve never — we and I think our competitors have consistently said in our view, that’s the bar for approval in the relapsed/refractory population. It’s going to be different in combination. And one of the things that we expect in combination is that we expect the duration for both populations, particularly the KMT2A to improve as we go to higher doses. But when we talk about the combinations, we’re going to set the bar a little bit differently.
But the fact that we had a 35% CR/CRH rate in the Phase Ib, again, don’t get emotionally attached to 35%. That’s great. You need to be 20% to 30%. But that Phase Ib data, coupled with the BTD award, I think, gives you confidence that we’re in the right ZIP code for being able to secure an approval for monotherapy. In terms of your question around resource allocation, we can do — we, Kura, on a go-alone basis, can probably pretty readily do one global pivotal trial. Now if we want to really blow out zifto and maximize the value, you’re talking about potentially multiple pivotal trials, including frontline, including maintenance, potentially solid tumors. We’ve said all along, they’re very likely will come a time when we need the resources, both financial and operational of a party larger than we are.
Running global pivotal trials is facilitated if you have people on the ground in all those different countries. But at the moment, we think we can drive really meaningful value for shareholders by just continuing to execute as we have. One of the things you want to understand is what’s the safety, tolerability, activity and some view into durability, both for NPM1 and KMT2A as you go to frontline because the longer that is, both — whether patients go to transplant or not, that’s going to help inform the commercial models. And really, we think, drive the value. So you’ll see us — we’re already actively evaluating what are different — how can we be clever. How can we take advantage of everything the health authorities have to offer, be efficient about the first combination pivotal trial, I think, we’re providing a really good foundation that will inspire physicians to have confidence that zifto can be used readily with these different combinations, right?
And that’s the starting point is you give them comfort that they can use it safely. It can be given orally once a day. There’s no other complications and then you just let the efficacy and the clinical activity speak for itself.
George Farmer: Okay. Thank you.
Operator: Thank you. There are no further questions at this time. I will now turn it back to Troy Wilson for closing remarks.
Troy Wilson: Great. Thank you. Thank you all once again for joining the call today. We’ll be participating in the Bank of America Healthcare Conference in a couple of weeks, and we look forward to seeing many of you there. In the meantime, if you have any additional questions, please feel free to contact Pete, Tom or me. Thank you, and have a good evening, everyone.
Operator: Thank you. Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.
